Progress in primary pulmonary hypertension (PPH) and familial primary pulmonary hypertension (FPPH) has led to the development of two general testable hypotheses. 1) Vasoactive mediators in PPH/FPPH will elucidate the pathogenesis of the vascular lesions and 2) restriction fragment length polymorphisms may yield insight into the location and type of genetic defect in FPPH.